The sub-acute toxicology of digoxin in dogs; clinical chemistry and histopathology of heart and kidneys

Abstract

Seventeen adult Beagle dogs received intravenous digoxin, over periods up to 30 days, at doses intended to induce minimal toxicity. The clinical signs of toxicity and ECG changes were as expected but, in contrast to other reports, the clinical chemistry changes (potassium, sodium, chloride, urea, creatinine) were not reliable indicators of morphological changes in the kidney. Similarly, the CPK or LDH rises did not correlate well with cardiac toxicity. All dogs but one showed rises in plasma alanine aminotransferase.

Only the few dogs which died early in the study showed microscopic evidence of cardiac changes, although sub-endocardial haemorrhage was observed in others. Dogs which did not suffer too great an initial insult, such as occurs with the traditional loading dose regimen, appeared to withstand repeated treatment with a clinically toxic dose, and sustain no microscopically detectable cardiotoxicity. Focal renal tubular necrosis was found in 10 out of 14 dogs whose kidneys were examined, and five of these showed no cardiac changes. The converse, cardiac without renal changes, was not found.